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Modified mRNA as an alternative to plasmid DNA (pDNA) for transcript replacement and vaccination therapy.

Youn H, Chung JK - Expert Opin Biol Ther (2015)

Bottom Line: Conversely, gene delivery using plasmid DNA (pDNA) is considered safer, but its transfection efficiency is much lower than virus-mediated gene transfer.Notable advantages include no risk of integration into the genomic DNA, adjustable gene expression and easier modulation of the immune system.By reducing or utilizing the immunogenic properties, mRNA offers a promising tool for gene/or transcript replacement.

View Article: PubMed Central - PubMed

Affiliation: Seoul National University, College of Medicine, Department of Nuclear Medicine , 103 Daehak-ro, Jongno-gu, Seoul 110-799 , Korea +82 2 2072 3341 ; +82 2 745 7690 ; jkchung@snu.ac.kr.

ABSTRACT

Introduction: Current gene therapy involves replacement of defective gene by delivery of healthy genetic material to precede normal function. Virus-mediated gene delivery is the most successful and efficient method for gene therapy, but it has been challenged due to serious safety concerns. Conversely, gene delivery using plasmid DNA (pDNA) is considered safer, but its transfection efficiency is much lower than virus-mediated gene transfer. Recently, mRNA has been suggested as an alternative option to avoid undesired insertion of delivered DNA sequences with higher transfection efficiency and stability.

Area covered: In this review, we summarize the currently available strategies of mRNA modification to increase the therapeutic efficacy; we also highlight the recent improvements of mRNA delivery for in vivo applications of gene therapy.

Expert opinion: The use of mRNA-based gene transfer could indeed be a promising new strategy for gene therapy. Notable advantages include no risk of integration into the genomic DNA, adjustable gene expression and easier modulation of the immune system. By reducing or utilizing the immunogenic properties, mRNA offers a promising tool for gene/or transcript replacement.

Show MeSH
Evaluating in vivo transfection efficiency of naked or nanoparticle-based modified (ARCA) mRNA according to the administration routes. A. Bioluminescence in C57BL/6 mice transfected intranasally with 4 μg of p/mLuc and n/mLuc over a 4-h time period. B. Bioluminescence in C57BL/6 mice transfected subcutaneously at the base of the ear pinna with p/mLuc and n/mLuc (in NaAc and RL) at 4 h. C. Bioluminescence signal in BALB/c mice intravenously administrated with 26 μg of p/mLuc and m/Luc at 8 h time points with respective color scales.
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Figure 0005: Evaluating in vivo transfection efficiency of naked or nanoparticle-based modified (ARCA) mRNA according to the administration routes. A. Bioluminescence in C57BL/6 mice transfected intranasally with 4 μg of p/mLuc and n/mLuc over a 4-h time period. B. Bioluminescence in C57BL/6 mice transfected subcutaneously at the base of the ear pinna with p/mLuc and n/mLuc (in NaAc and RL) at 4 h. C. Bioluminescence signal in BALB/c mice intravenously administrated with 26 μg of p/mLuc and m/Luc at 8 h time points with respective color scales.

Mentions: Recently, transfection efficiency and transgene expression using mRNA by various injection routes have also been intensively investigated [69,70]. Figure 5 shows bioluminescence imaging to evaluate in vivo transection efficiency of naked or nanoparticle (ovalbumin)-based mRNA with chemical modification (ARCA) mRNA delivery. Transfection was increased by OVA nanoparticle-mediated mRNA transfer compared to naked mRNA both in intranasal and i.v. injections.


Modified mRNA as an alternative to plasmid DNA (pDNA) for transcript replacement and vaccination therapy.

Youn H, Chung JK - Expert Opin Biol Ther (2015)

Evaluating in vivo transfection efficiency of naked or nanoparticle-based modified (ARCA) mRNA according to the administration routes. A. Bioluminescence in C57BL/6 mice transfected intranasally with 4 μg of p/mLuc and n/mLuc over a 4-h time period. B. Bioluminescence in C57BL/6 mice transfected subcutaneously at the base of the ear pinna with p/mLuc and n/mLuc (in NaAc and RL) at 4 h. C. Bioluminescence signal in BALB/c mice intravenously administrated with 26 μg of p/mLuc and m/Luc at 8 h time points with respective color scales.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4696419&req=5

Figure 0005: Evaluating in vivo transfection efficiency of naked or nanoparticle-based modified (ARCA) mRNA according to the administration routes. A. Bioluminescence in C57BL/6 mice transfected intranasally with 4 μg of p/mLuc and n/mLuc over a 4-h time period. B. Bioluminescence in C57BL/6 mice transfected subcutaneously at the base of the ear pinna with p/mLuc and n/mLuc (in NaAc and RL) at 4 h. C. Bioluminescence signal in BALB/c mice intravenously administrated with 26 μg of p/mLuc and m/Luc at 8 h time points with respective color scales.
Mentions: Recently, transfection efficiency and transgene expression using mRNA by various injection routes have also been intensively investigated [69,70]. Figure 5 shows bioluminescence imaging to evaluate in vivo transection efficiency of naked or nanoparticle (ovalbumin)-based mRNA with chemical modification (ARCA) mRNA delivery. Transfection was increased by OVA nanoparticle-mediated mRNA transfer compared to naked mRNA both in intranasal and i.v. injections.

Bottom Line: Conversely, gene delivery using plasmid DNA (pDNA) is considered safer, but its transfection efficiency is much lower than virus-mediated gene transfer.Notable advantages include no risk of integration into the genomic DNA, adjustable gene expression and easier modulation of the immune system.By reducing or utilizing the immunogenic properties, mRNA offers a promising tool for gene/or transcript replacement.

View Article: PubMed Central - PubMed

Affiliation: Seoul National University, College of Medicine, Department of Nuclear Medicine , 103 Daehak-ro, Jongno-gu, Seoul 110-799 , Korea +82 2 2072 3341 ; +82 2 745 7690 ; jkchung@snu.ac.kr.

ABSTRACT

Introduction: Current gene therapy involves replacement of defective gene by delivery of healthy genetic material to precede normal function. Virus-mediated gene delivery is the most successful and efficient method for gene therapy, but it has been challenged due to serious safety concerns. Conversely, gene delivery using plasmid DNA (pDNA) is considered safer, but its transfection efficiency is much lower than virus-mediated gene transfer. Recently, mRNA has been suggested as an alternative option to avoid undesired insertion of delivered DNA sequences with higher transfection efficiency and stability.

Area covered: In this review, we summarize the currently available strategies of mRNA modification to increase the therapeutic efficacy; we also highlight the recent improvements of mRNA delivery for in vivo applications of gene therapy.

Expert opinion: The use of mRNA-based gene transfer could indeed be a promising new strategy for gene therapy. Notable advantages include no risk of integration into the genomic DNA, adjustable gene expression and easier modulation of the immune system. By reducing or utilizing the immunogenic properties, mRNA offers a promising tool for gene/or transcript replacement.

Show MeSH